Process-Based Modeling of Phenology and Radial Growth in Pinus tabuliformis in Response to Climate Factors over a Cold and Semi-Arid Region.

(1) Background: Climate change significantly impacts the phenology and dynamics of radial tree growth in alpine dryland forests. However, there remains a scarcity of reliable information on the physiological processes of tree growth and cambial phenology in response to long-term climate change in cold and semi-arid regions. (2) Methods: We employed the process-based Vaganov-Shashkin (VS) model to simulate the phenology and growth patterns of Chinese pine (Pinus tabuliformis) in the eastern Qilian Mountains, northeastern Tibetan Plateau. The model was informed by observed temperature and precipitation data to elucidate the relationships between climate factors and tree growth. (3) Results: The simulated tree-ring index closely aligned with the observed tree-ring chronology, validating the VS model's effectiveness in capturing the climatic influences on radial growth and cambial phenology of P. tabuliformis. The model outputs revealed that the average growing season spanned from mid-April to mid-October and experienced an extension post-1978 due to ongoing warming trends. However, it is important to note that an increase in the duration of the growing season did not necessarily result in a higher level of radial growth. (4) Conclusions: While the duration of the growing season was primarily determined by temperature, the growth rate was predominantly influenced by water conditions during the growing season, making it the most significant factor contributing to ring formation. Our study provides valuable insights into the potential mechanisms underlying tree growth responses to climate change in cold and semi-arid regions.

Predictive value of volumetric parameters based on 18F-PSMA-1007 PET/CT for prostate cancer metastasis.

Purpose of the report: To explore the value of 18F-labeled prostate-specific membrane antigen (PSMA-1007) positron emission tomography (PET)/computed tomography (CT), the maximum standardized uptake value (SUVmax) of the primary tumor, prostate PSMA-tumor volume (PSMA-TVp), and prostate total lesion PSMA (TL-PSMAp) for predicting prostate cancer (PCa) metastasis and follow-up evaluation in primary PCa lesions. Materials and methods: 18F-PSMA-1007 PET/CT data of 110 consecutive newly diagnosed PCa patients were retrospectively analyzed. Patients were divided into non-metastatic, oligometastatic, and extensive metastatic groups. The predictive power was assessed using the receiver operating characteristic curve. Multi-group one-way analysis of variance and post-hoc tests were used to compare the groups. Patients were monitored post-therapy to evaluate treatment effectiveness. Results: Among the 110 patients, 66.4% (73) had metastasis (29 oligometastatic, 44 extensive metastasis). AUCs for Gleason score (GS), total prostate-specific antigen(TPSA), SUVmax, TL-PSMAp, and PSMA-TVp were 0.851, 0.916, 0.834, 0.938, and 0.923, respectively. GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp were significantly different among the groups. In the post-hoc tests, differences in GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp between the non-metastatic and oligometastatic groups and non-metastatic and extensive metastatic groups were significant (P<0.010). Differences in TL-PSMAp and PSMA-TVp between oligometastatic and extensive metastatic groups were significant (P=0.039 and 0.015, respectively), while those among GS, TPSA, and SUVmax were not. TL-PSMAp and PSMA-TVp distinguished between oligometastatic and extensive metastases, but GS, TPSA, and SUVmax did not. In individuals with oligometastasis, the implementation of active treatment for both primary and metastatic lesions may result in a more favorable prognosis. Conclusions: 18F-PSMA-1007 PET/CT volumetric parameters PSMA-TVp and TL-PSMAp can predict PCa oligometastasis.

18F-FDG PET/CT Findings of Tibia Metastasis From Endometrial Adenocarcinoma.

ABSTRACT: Bone metastases from endometrial carcinoma are rare, especially when the bone is the sole metastatic site. A 55-year-old woman with a history of endometrial carcinoma was referred for FGD PET/CT scan due to pain in the left knee. The images showed that multiple lesions with intense activity were detected in the left tibia. Histopathological examination and immunohistochemistry of the left tibial lesion confirmed metastases from the endometrial adenocarcinoma.

Increasing forest carbon sinks in cold and arid northeastern Tibetan Plateau.

Arid forest lands account for 6 % of the world's forest area, but their carbon density and carbon storage capacity have rarely been assessed. Forest inventories provide estimates of forest stock and biomass carbon density, improve our understanding of the carbon cycle, and help us develop sustainable forest management policies in the face of climate change. Here, we carried out three forest inventories at five-year intervals from 2006 to 2016 in 104 permanent sample plots covering the Qinghai spruce (Picea crassifolia) distribution in the north slope of Qilian Mountains, northeastern Tibetan Plateau. Results shows that mean biomasses for Qinghai spruce were 133.80, 144.89, and 157.01 Mg ha-1 while biomass carbon densities were 65.52, 70.92, and 76.88 Mg C ha-1, in 2006, 2011, and 2016, respectively. This shows an increase in the Qinghai spruce carbon density of 17.34 % from 2006 to 2016. Both the precipitation and temperature play crucial roles on the increase of aboveground carbon density. The average carbon densities were different among forests with different ages and were higher for older forests. Our results show that the carbon sequestration rate for Qinghai spruce in the Qilian Mountains is significantly higher than the average rates of national forest parks in China, suggesting that this spruce forest has the potential to sequester a significant amount of carbon despite the general harsh growing conditions of cold and arid ecoregions. Our findings provide important insights that are helpful for the assessment of forest carbon for cold and arid lands.

The past, present, and future of ecogeographic isolation between closely related Aquilegia plants.

Quantifying the strength of the ecogeographic barrier is an important aspect of plant speciation research, and serves as a practical step to understanding the evolutionary trajectory of plants under climate change. Here, we quantified the extent of ecogeographic isolation in four closely related Aquilegia species that radiated in the Mountains of SW China and adjacent regions, often lacking intrinsic barriers. We used environmental niche models to predict past, present, and future species potential distributions and compared them to determine the degree of overlap and ecogeographic isolation. Our investigation found significant ecological differentiation in all studied species pairs except A. kansuensis and A. ecalacarata. The current strengths of ecogeographic isolation are above 0.5 in most cases. Compared with current climates, most species had an expanding range in the Last Glacial Maximum, the Mid Holocene, and under four future climate scenarios. Our results suggested that ecogeographic isolation contributes to the diversification and maintenance of Aquilegia species in the Mountains of northern and SW China and would act as an essential reproductive barrier in the future.

Interdependent Nuclear Co-Trafficking of ASPP1 and p53 Aggravates Cardiac Ischemia/Reperfusion Injury.

OBJECTIVE: ASPP1 (apoptosis stimulating of p53 protein 1) is critical in regulating cell apoptosis as a cofactor of p53 to promote its transcriptional activity in the nucleus. However, whether cytoplasmic ASPP1 affects p53 nuclear trafficking and its role in cardiac diseases remains unknown. This study aims to explore the mechanism by which ASPP1 modulates p53 nuclear trafficking and the subsequent contribution to cardiac ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: The immunofluorescent staining showed that under normal condition ASPP1 and p53 colocalized in the cytoplasm of neonatal mouse ventricular cardiomyocytes, while they were both upregulated and translocated to the nuclei upon hypoxia/reoxygenation treatment. The nuclear translocation of ASPP1 and p53 was interdependent, as knockdown of either ASPP1 or p53 attenuated nuclear translocation of the other one. Inhibition of importin-ß1 resulted in the cytoplasmic sequestration of both p53 and ASPP1 in neonatal mouse ventricular cardiomyocytes with hypoxia/reoxygenation stimulation. Overexpression of ASPP1 potentiated, whereas knockdown of ASPP1 inhibited the expression of Bax (Bcl2-associated X), PUMA (p53 upregulated modulator of apoptosis), and Noxa, direct apoptosis-associated targets of p53. ASPP1 was also increased in the I/R myocardium. Cardiomyocyte-specific transgenic overexpression of ASPP1 aggravated I/R injury as indicated by increased infarct size and impaired cardiac function. Conversely, knockout of ASPP1 mitigated cardiac I/R injury. The same qualitative data were observed in neonatal mouse ventricular cardiomyocytes exposed to hypoxia/reoxygenation injury. Furthermore, inhibition of p53 significantly blunted the proapoptotic activity and detrimental effects of ASPP1 both in vitro and in vivo. CONCLUSIONS: Binding of ASPP1 to p53 triggers their nuclear cotranslocation via importin-ß1 that eventually exacerbates cardiac I/R injury. The findings imply that interfering the expression of ASPP1 or the interaction between ASPP1 and p53 to block their nuclear trafficking represents an important therapeutic strategy for cardiac I/R injury.

99mTc-labeled iRGD for single-positron emission computed tomography imaging of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with a high mortality rate. One of the main reasons for this poor prognosis is the failure of a specific diagnosis. As a tumor-homing and penetrating peptide, iRGD has not only the properties of binding to neuropilin-1 and integrin αvß3 but also internalizing into TNBC cells. In this study, we designed and prepared 99mTc-labeled iRGD (99mTc-HYNIC-iRGD) as a single-positron emission computed tomography (SPECT) imaging probe and investigated its feasibility for the targeted diagnosis of TNBC. The results showed that the iRGD peptide had acceptable biocompatibility within the studied concentration range and could specifically bind to TNBC cells in vitro. The 99mTc-HYNIC-iRGD was readily prepared with high radiochemical purity and stability. SPECT imaging of 99mTc-HYNIC-iRGD in a TNBC tumor-bearing mouse model showed obvious tumor accumulation with rapid blood clearance and favorable biodistribution. Our findings indicate that this active-targeted strategy has great potential to be developed as a novel tool for TNBC imaging.

Cytoplasmic sequestration of p53 by lncRNA-CIRPILalleviates myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (MI/R) injury is a pathological process that seriously affects the health of patients with coronary artery disease. Long non-coding RNAs (lncRNAs) represents a new class of regulators of diverse biological processes and disease conditions, the study aims to discover the pivotal lncRNA in MI/R injury. The microarray screening identifies a down-regulated heart-enriched lncRNA-CIRPIL (Cardiac ischemia reperfusion associated p53 interacting lncRNA, lncCIRPIL) from the hearts of I/R mice. LncCIRPIL inhibits apoptosis of cultured cardiomyocytes exposed to anoxia/reoxygenation (A/R). Cardiac-specific transgenic overexpression of lncCIRPIL alleviates I/R injury in mice, while knockout of lncCIRPIL exacerbates cardiac I/R injury. LncCIRPIL locates in the cytoplasm and physically interacts with p53, which leads to the cytoplasmic sequestration and the acceleration of ubiquitin-mediated degradation of p53 triggered by E3 ligases CHIP, COP1 and MDM2. p53 overexpression abrogates the protective effects of lncCIRPIL. Notably, the human fragment of conserved lncCIRPIL mimics the protective effects of the full-length lncCIRPIL on cultured human AC16 cells. Collectively, lncCIRPIL exerts its cardioprotective action via sequestering p53 in the cytoplasm and facilitating its ubiquitin-mediated degradation. The study highlights a unique mechanism in p53 signal pathway and broadens our understanding of the molecular mechanisms of MI/R injury.

[99mTc]Tc-Labeled Plectin-Targeting Peptide as a Novel SPECT Probe for Tumor Imaging.

Certain receptors are often overexpressed during tumor occurrence and development and closely correlate with carcinogenesis. Owing to its overexpression on the cell membrane and cytoplasm of various tumors, plectin, which is involved in tumor proliferation, migration, and invasion, has been viewed as a promising target for cancer imaging. Hence, plectin-targeting agents have great potential as imaging probes for tumor diagnosis. In this study, we developed a [99mTc]Tc-labeled plectin-targeted peptide (PTP) as a novel single-photon emission computed tomography (SPECT) probe for tumor imaging and investigated its pharmacokinetics, biodistribution, and targeting ability in several types of tumor-bearing mouse models. The PTP had good biocompatibility and targeting ability to tumor cells in vitro and could be readily labeled with [99mTc]Tc after modification with the bifunctional chelator 6-hydrazino nicotinamide (HYNIC). Furthermore, the prepared [99mTc]Tc-labeled PTP ([99mTc]Tc-HYNIC-PTP) showed high radiochemical purity and excellent stability in vitro. In addition, favorable biodistribution, fast blood clearance, and clear accumulation of [99mTc]Tc-HYNIC-PTP in several types of tumors were observed, with a good correlation between tumor uptake and plectin expression levels. These results indicate the potential of [99mTc]Tc-HYNIC-PTP as a novel SPECT probe for tumor imaging.

131I-Labeled Multifunctional Polyethylenimine/Doxorubicin Complexes with pH-Controlled Cellular Uptake Property for Enhanced SPECT Imaging and Chemo/Radiotherapy of Tumors.

INTRODUCTION: Smart theranostic nanosystems own a favorable potential to improve internalization within tumor while avoiding nonspecific interaction with normal tissues. However, development of this type of theranostic nanosystems is still a challenge. METHODS: In this study, we developed the iodine-131 (131I)-labeled multifunctional polyethylenimine (PEI)/doxorubicin (DOX) complexes with pH-controlled cellular uptake property for enhanced single-photon emission computed tomography (SPECT) imaging and chemo/radiotherapy of tumors. Alkoxyphenyl acylsulfonamide (APAS), a typical functional group that could achieve improved cellular uptake of its modified nanoparticles, was utilized to conjugate onto the functional PEI pre-modified with polyethylene glycol (PEG) with terminal groups of monomethyl ether and N-hydroxysuccinimide (mPEG-NHS), PEG with terminal groups of maleimide and succinimidyl valerate (MAL-PEG-SVA) through sulfydryl of APAS and MAL moiety of MAL-PEG-SVA. This was followed by conjugation with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), acetylating leftover amines of PEI, complexing DOX and labeling 131I to generate the theranostic nanosystems. RESULTS: The synthesized theranostic nanosystems exhibit favorable water solubility and stability. Every functional PEI can complex approximately 12.4 DOX, which could sustainably release of DOX following a pH-dependent manner. Remarkably, due to the surface modification of APAS, the constructed theranostic nanosystems own the capacity to achieve pH-responsive charge conversion and further lead to improved cellular uptake in cancer cells under slightly acidic condition. Above all, based on the coexistence of DOX and radioactive 131I in the single nanosystem, the synthesized nanohybrid system could afford enhanced SPECT imaging and chemo/radioactive combination therapy of cancer cells in vitro and xenografted tumor model in vivo. DISCUSSION: The developed smart nanohybrid system provides a novel strategy to improve the tumor theranostic efficiency and may be applied for different types of cancer.

The long noncoding RNA lncCIRBIL disrupts the nuclear translocation of Bclaf1 alleviating cardiac ischemia-reperfusion injury.

Cardiac ischemia-reperfusion (I/R) injury is a pathological process resulting in cardiomyocyte death. The present study aims to evaluate the role of the long noncoding RNA Cardiac Injury-Related Bclaf1-Inhibiting LncRNA (lncCIRBIL) on cardiac I/R injury and delineate its mechanism of action. The level of lncCIRBIL is reduced in I/R hearts. Cardiomyocyte-specific transgenic overexpression of lncCIRBIL reduces infarct area following I/R injury. Knockout of lncCIRBIL in mice exacerbates cardiac I/R injury. Qualitatively, the same results are observed in vitro. LncCIRBIL directly binds to BCL2-associated transcription factor 1 (Bclaf1), to inhibit its nuclear translocation. Cardiomyocyte-specific transgenic overexpression of Bclaf1 worsens, while partial knockout of Bclaf1 mitigates cardiac I/R injury. Meanwhile, partial knockout of Bclaf1 abrogates the detrimental effects of lncCIRBIL knockout on cardiac I/R injury. Collectively, the protective effect of lncCIRBIL on I/R injury is accomplished by inhibiting the nuclear translocation of Bclaf1. LncCIRBIL and Bclaf1 are potential therapeutic targets for ischemic cardiac disease.

Polyethylenimine-based theranostic nanoplatform for glioma-targeting single-photon emission computed tomography imaging and anticancer drug delivery.

BACKGROUND: Glioma is the deadliest brain cancer in adults because the blood-brain-barrier (BBB) prevents the vast majority of therapeutic drugs from entering into the central nervous system. The development of BBB-penetrating drug delivery systems for glioma therapy still remains a great challenge. In this study, we aimed to design and develop a theranostic nanocomplex with enhanced BBB penetrability and tumor-targeting efficiency for glioma single-photon emission computed tomography (SPECT) imaging and anticancer drug delivery. RESULTS: This multifunctional nanocomplex was manufactured using branched polyethylenimine (PEI) as a template to sequentially conjugate with methoxypolyethylene glycol (mPEG), glioma-targeting peptide chlorotoxin (CTX), and diethylenetriaminepentaacetic acid (DTPA) for 99mTc radiolabeling on the surface of PEI. After the acetylation of the remaining PEI surface amines using acetic anhydride (Ac2O), the CTX-modified PEI (mPEI-CTX) was utilized as a carrier to load chemotherapeutic drug doxorubicin (DOX) in its interior cavity. The formed mPEI-CTX/DOX complex had excellent water dispersibility and released DOX in a sustainable and pH-dependent manner; furthermore, it showed targeting specificity and therapeutic effect of DOX toward glioma cells in vitro and in vivo (a subcutaneous tumor mouse model). Owing to the unique biological properties of CTX, the mPEI-CTX/DOX complex was able to cross the BBB and accumulate at the tumor site in an orthotopic rat glioma model. In addition, after efficient radiolabeling of PEI with 99mTc via DTPA, the 99mTc-labeled complex could help to visualize the drug accumulation in tumors of glioma-bearing mice and the drug delivery into the brains of rats through SPECT imaging. CONCLUSIONS: These results indicate the potential of the developed PEI-based nanocomplex in facilitating glioma-targeting SPECT imaging and chemotherapy.

The role of CT in PET/CT for assessing diffuse infiltration of bone marrow in multiple myeloma using the Durie-Salmon PLUS staging system.

PET/CT has been identified as one of the routine methods for the assessment of multiple myeloma (MM) bone marrow infiltration. In the routine method of performing PET/CT, the 18F-Fludeoxyglucose (18F-FDG) uptake in this disease is often used in the assessment of this condition, however CT diagnosis is not currently commonly used. The aim of the present study was to investigate the importance of CT in PET/CT for assessing diffuse infiltration (DI) of bone marrow in MM. MRI was used as a control in the present study, which is the gold standard for assessing DI of bone marrow and is divided into 3 levels: Mild, moderate and severe DI. Subsequently, a total of four combinations of PET and CT results were listed using the enumeration method for the evaluation of DI in the bone marrow. These combinations were respectively compared with the three levels of MR imaging to screen the most consistent method. The concordances of the new method and routine 18F-FDG PET/CT for the assessment of DI with MR imaging were compared using the McNemar test, respectively. The results of the DI assessment from the two methods were verified by performing Durie-Salmon (D-S) PLUS staging. Compared with MR imaging, the results were as follows: PET and CT exhibited negative results, suggesting mild DI; one of them was positive, suggesting moderate DI; and two were positive, suggesting severe DI. The results of concordance between two methods (new and routine) and MR imaging are indicated as follows: For the new method, McNemar test, P=0.513 and Kappa=0.745; for the routine 18F-FDG PET/CT method, McNemar test, P=0.03 and Kappa=0.547. Re-performance of D-S PLUS staging presented the following results: New method, McNemar test, P=0.317 and Kappa=0.93; for the routine method, McNemar test, P=0.223 and Kappa=0.811. These findings indicated that the CT component of PET/CT could improve the concordance with MRI results in the assessment of DI, and the same results were obtained when D-S PLUS staging was performed. The CT in PET/CT can enhance diagnostic accuracy in the assessment of DI by reducing the false negatives when compared with the routine 18F-FDG method.

LyP-1-Modified Multifunctional Dendrimers for Targeted Antitumor and Antimetastasis Therapy.

We designed and synthesized 131I-labeled dendrimers modified with the LyP-1 peptide as a multifunctional platform for single-photon emission computed tomography (SPECT) imaging, radionuclide therapy, and antimetastasis therapy of cancer. The multifunctional platform was constructed by modifying amine-terminated generation 5 poly(amidoamine) dendrimers with 33.1 LyP-1 peptide and 9.2 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO), followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I via the HPAO moieties. The LyP-1-modified dendrimers showed favorable cytocompatibility in the studied concentration range of 0.1-10 µM for 24 h and could be labeled by 131I with satisfactory radiochemical purity (>99%) and stability (>90% even at 16 h). The 131I-labeled LyP-1-modified dendrimers were capable of being utilized as a diagnostic probe for SPECT imaging and as a therapeutic agent for radionuclide therapy and antimetastasis of cancer cells in vitro and in a subcutaneous tumor model in vivo. Based on analyses of the tumor microenvironment, the antitumor and antimetastasis effects could be because of the reduced levels of the molecular markers associated with proliferation and metastasis, improved local hypoxia, and increased apoptosis rate. The developed 131I-labeled dendrimeric nanodevice may hold great promise to be used as a nanotheranostic platform for cancer diagnosis and therapy.

Hyperparathyroidism Due to Concurrent Parathyroid Carcinoma and Parathyroid Adenoma.

Parathyroid carcinoma is uncommon, and its coexistence with parathyroid adenoma is extremely rare. A 28-year-old woman with hyperparathyroidism underwent dual-phase Tc-sestamibi SPECT/CT scan for presurgical evaluation. The images showed intense activity inside the left side thyroid and mild activity inside the right side of the thyroid. The histopathologic findings showed intrathyroidal parathyroid carcinoma on the left side and intrathyroid parathyroid adenoma on the right side.

Water mediates fertilization in a terrestrial flowering plant.

Water-mediated fertilization is ubiquitous in early land plants. This ancestral mode of fertilization has, however, generally been considered to have been lost during the evolutionary history of terrestrial flowering plants. We investigated reproductive mechanisms in the subtropical ginger Cautleya gracilis (Zingiberaceae), which has two pollen conditions - granular and filiform masses - depending on external conditions. We tested whether rain transformed granular pollen into filiform masses and whether this then promoted pollen-tube growth and fertilization of ovules. Using experimental manipulations in the field we investigated the contribution of water-mediated fertilization to seed production. Rain caused granular pollen to form filiform masses of germinating pollen tubes, which transported sperm to ovules, resulting in fertilization and seed set. Flowers exposed to rain produced significantly more seeds than those protected from the rain, which retained granular pollen. Insect pollination made only a limited contribution to seed set because rainy conditions limited pollinator service. Our results reveal a previously undescribed fertilization mechanism in flowering plants involving water-mediated fertilization stimulated by rain. Water-mediated fertilization is likely to be adaptive in the subtropical monsoon environments in which C. gracilis occurs by ensuring reproductive assurance when persistent rain prevents insect-mediated pollination.

Correlation between the timing of autonomous selfing and floral traits: a comparative study from three selfing Gentianopsis species (Gentianaceae).

About 20% of angiosperms employ self-fertilization as their main mating strategy. In this study, we aimed to examine how the selfing timing correlated with floral traits in three Gentianopsis species in which autonomous selfing is achieved through filament elongation. Although the three Gentianopsis species exhibit no significant variation in their capacity for autonomous selfing, flowers of G. grandis last longer, are larger and have a higher corolla biomass, P/O ratios and male biomass allocation than those of G. paludosa, and especially those of G. contorta. Autonomous selfing occurs in the early floral life of G. paludosa and G. contorta and in the later floral life of G. grandis. Seed production mainly results from autonomous selfing in G. paludosa and G. contorta; however, G. grandis could be more described as having a mixed mating system. We suggest that autonomous selfing in later floral life increases the chance of cross-pollination prior to this, while autonomous selfing in early floral life offers a selective advantage to plants by reducing the resource investment in traits that may increase pollinator attraction and visitation.

MnSOD up-regulates maspin tumor suppressor gene expression in human breast and prostate cancer cells.

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme with tumor suppressor activity; however, the molecular mechanisms of MnSOD antitumor effects remain unclear. We hypothesized that MnSOD activity in cancer cells might cause downstream changes in the expression of other tumor suppressor genes. To determine whether maspin, a tumor suppressor gene that inhibits breast cancer cell invasion and metastasis, might be a target of MnSOD, we forced MnSOD expression in several human breast and prostate cancer cell lines by adenovirus-mediated gene transfer and measured maspin mRNA expression. Forced expression of MnSOD caused maspin mRNA to accumulate in a dose-dependent manner in both human breast and prostate cancer cells. Normal p53 was not necessary to mediate the effect of MnSOD because MnSOD up-regulated maspin in cells that harbor wild-type p53 and in cells that harbor mutant p53. Moreover, the effects of MnSOD on maspin were not due to demethylation of the maspin promoter. Analyses of maspin promoter activity, transcriptional run-on, and mRNA stability showed that maspin mRNA stability was the major mechanism for maspin up-regulation by MnSOD. Our findings identify a mechanism underlying MnSOD antitumor effects and provide evidence to support MnSOD as a genetic therapy in the treatment of human breast and prostate cancers.